This award is made as the starter grant increment of Dr. Richard Gibbs' Postdoctoral Research Fellowship in Chemistry Award in support of his research at Wayne State University. The research is concerned with chemical reactions modifying ras proteins, which are present in virtually all eukaryotic cells and are believed to be critical in signal transduction. The chemical reactions which Gibbs will study are related to transformations thought to be essential to ras protein activity in living systems, including farnesylation of a cysteine function, cleavage of three c-terminal amino acids, and methylation of a cysteine carboxylate function. An assay system will be developed for the protease involved, the protease will be characterized, and an enzyme inhibitor will be designed and synthesized. The synthesis of a Ras protease inhibitor would provide a valuable tool for the further study of post-translational modifications of the ras protein.
